Campus & Community

HMS researchers boost blood cancer fight

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Hormone injections increase stem cell production

David Scadden (left), associate professor at HMS, works at a fluorescent activated cell sorter with instructor Gregor Adams. (Staff photo Jon Chase/Harvard News Office)

Harvard researchers have stimulated mice to increase their production of blood stem cells, a development with apparent human parallels that researchers hope will have immediate benefits in the treatment of blood cancers.

If it works in humans as in mice, the advance could provide additional hope for patients suffering from leukemia, myeloma, or lymphoma who need bone marrow transplants.

The researchers, largely based at Massachusetts General Hospital’s (MGH) Center for Regenerative Medicine and Technology, have begun setting up a phase 2 trial to test their findings in human subjects. They predict the trial will begin early next year.

Working with colleagues at the University of Rochester School of Medicine, researchers found that giving mice a hormone known for building bones increased their production of blood stem cells.

Blood stem cells, which grow into different kinds of blood cells, are critical in the treatment of blood cancers. These cancers are sometimes treated by radiation that kills the cancerous cells in the bone marrow, which is where blood cells grow. New stem cells are then transplanted into the bone marrow where they take over production of blood from the cancerous cells.

Stem cell transplant patients fall roughly into two categories, according to Associate Professor of Medicine David Scadden, director of MGH’s Center for Regenerative Medicine and Technology.

Some patients can have their own stem cells transplanted back into them, though it is sometimes difficult to get enough cells to perform the procedure. If the parathyroid hormone treatment is effective in humans, it could be given to these patients to increase their body’s production of these stem cells, which could then be extracted and used in the transplant.

A second group of patients can only use cells from donors, though finding compatible donors is difficult. Roughly a third of them cannot find a compatible donor at all. For that third, researchers are currently exploring the use of umbilical cord derived blood stem cells, but currently there’s too few of them to be useful for adult transplants.

Scadden and his colleagues’ research indicated that, coupled with parathyroid hormone treatments, it may be possible to use fewer stem cells in a transplant. That would make transplants with fewer cells, as would occur in the use of umbilical cord cells, a safer procedure.

Whatever the case, either having more stem cells available for transplant or needing fewer would benefit patients, Scadden said.

All can potentially benefit from increasing their body’s supply of blood stem cells, which would, in turn, reduce the number of cells needed for transplantation.

Bones and marrow

Science has long known that the bone marrow is where blood cells are born. Researchers in Scadden’s group focused on the area where the marrow meets the bone. They knew that blood stem cells originated there and moved toward the middle of the marrow as they changed into different types of blood cells.

They also knew that bone tissue originated in roughly the same place, created by cells called osteoblasts. Researchers reasoned that the two processes weren’t in the same place by accident and must be linked.

If that was the case, they thought, stimulating bone tissue creation using the parathyroid hormone may also stimulate the production of blood stem cells. Researchers performed several experiments that verified their hunch.

Perhaps the most dramatic was when researchers simulated the situation of a patient needing a stem cell transplant. They first used radiation to destroy the bone marrow of laboratory mice and then transplanted stem cells to take the place of the cells that had been killed. Some of the mice received injections of parathyroid hormone while others, a control group, did not.

All of the mice that received treatment with the parathyroid hormone survived. Only 27 percent of the control group survived.

“We were quite surprised by the magnitude of the response,” Scadden said. “To have [results] go from 72 or 73 percent mortality to zero percent mortality is extraordinary.”

The study was published in the Oct. 23 issue of the journal Nature.

The hormone involved in the study is currently approved for use in humans as a treatment for osteoporosis. This existing approval allows researchers to skip the extensive safety trials needed when new drugs are used on humans and move right into testing for effectiveness.

Scadden credited interdisciplinary work between teams of cell biologists and endocrinologists at MGH and at the University of Rochester, particularly Laura Calvi, formerly of the MGH Endocrinology Unit, and Gregor Adams from MGH, a research fellow at Harvard Medical School.

The approach taken by the team, in which they examine cells known to operate in regions where blood stem cells form, could be fruitful in research on other types of stem cells, Scadden said.